Regulatory t cells targeted with chimeric antigen receptors

Abstract

Regulatory T cells (Treg) are engineered to express a chimeric antigen receptor (CAR), that specifically binds folate receptor beta; and are administered to an individual for treatment of inflammation at sites characterized by the presence of activated myeloid cells. Also provided are methods for utilized engineered T regulatory cells to enhance hematopoietic cell transplantation.

What is claimed is: 
     
         1 . A method for treating an inflammatory condition in a subject in need thereof, comprising administering to said subject:
 an effective dose of regulatory T cells (Treg) engineered to express a chimeric antigen receptor (CAR), that specifically binds folate receptor beta (FRβ);   wherein inflammation is decreased at the targeted site.   
     
     
         2 . The method of  claim 1 , wherein the CAR directly binds to FRβ. 
     
     
         3 . The method of  claim 1 , wherein the CAR specifically binds to a small molecule non-endogenous antigenic moiety; and is administered in combination with an effective dose of targeting antibodies, which antibodies (i) bind to FRβ and (ii) are labeled with the non-endogenous antigenic moiety. 
     
     
         4 . The method of  claim 3 , wherein the antigenic moiety is fluorescein isothiocyanate (FITC). 
     
     
         5 . The method of  claim 1 , wherein the Treg cells are isolated from a peripheral blood sample. 
     
     
         6 . The method of  claim 1 , wherein the Treg cells are expanded in culture. 
     
     
         7 . The method of  claim 1 , wherein the subject is a human. 
     
     
         8 . The method of  claim 1 , where the inflammatory condition is diabetes. 
     
     
         9 . The method of  claim 8 , wherein the diabetes is Type 2 diabetes. 
     
     
         10 . The method of  claim 9 , wherein obesity is reduced following administration of the regulatory T cells. 
     
     
         11 . The method of  claim 9 , wherein insulin resistance is decreased following administration of the regulatory T cells. 
     
     
         12 . The method of  claim 1 , wherein the inflammatory condition is inflammatory bowel disease. 
     
     
         13 . The method of  claim 12 , wherein colitis is decreased following administration of the regulatory T cells. 
     
     
         14 . A cellular composition of engineered Treg cells for use in the method of  claim 1 . 
     
     
         15 . A kit comprising the cellular composition of  claim 14 , and a suitable targeting antibody. 
     
     
         16 . A method for enhancing chimerism of a recipient following hematopoietic cell transplantation (HCT), comprising:
 administering to said subject an effective dose of regulatory T cells (Treg) engineered to express a chimeric antigen receptor (CAR), that specifically binds a protein involved in hematopoietic stem cell migration and/or homing; in combination with an effective dose of hematopoietic stem cells.   
     
     
         17 . The method of  claim 16 , wherein the transplant recipient has been treated with myeloablative conditioning regimen prior to administering the Treg and hematopoietic stem cells. 
     
     
         18 . The method of  claim 16 , wherein the protein involved in hematopoietic stem cell migration and/or homing is SDF-1. 
     
     
         19 . The method of  claim 16 , wherein the protein involved in hematopoietic stem cell migration and/or homing is MHC Class I protein. 
     
     
         20 . The method of  claim 16 , wherein the hematopoietic cell sample is obtained from bone marrow, from cord blood, or by apheresis from mobilized peripheral blood.